Fluid analyzing apparatus

ABSTRACT

A fluid sample analysis instrument includes two sample chambers with an electrode assembly associated with each sample chamber. The instrument includes a common pump system for applying reduced pressure to the sample chambers to produce flow of fluid into and out of the sample chambers and a common circulator system for circulating fluid past the electrode assemblies and sample chambers to maintain the sample chambers and electrode assemblies at a pre-established temperature.

United States Patent Spergel et al. [451 Apr. 25, 1972 FLUID ANALYZINGAPPARATUS References Cited [72] Inventors: Philip Spergel, Lexington;Stanley L. UNITED STATES PATENTS Games waylafldi Wmi'm Maxwell,3,556,950 1/1971 'Dahms ..23/253 x boro; Ronald McFayden, Wfillh3,560,161 2/l971 Webb ......23/253 Thom Rom, Lexmswn; David 3,250,1186/l966 Johnson, Jr. ..23/25s x Blnckmer, Harvard, all of Mass. [73]Assignee: instrumentation Laboratory, lnc., Lexing- Primary 'f' f' Pscmronek on, Mass. Attorney-Wrlhs M. Ertman Filed: l"- 7, 1970 [57]ABSTRACT PP- 271200 A fluid sample analysis instrument includes twosample chambers withan electrode assembly associated with each sample[52] U 5 Cl 23/253 R 23/255 E 324/30 chamber. The instrument includes acommon pump system for 264/195 applying reduced pressure to the samplechambers to produce [5 I] Int Cl G01 27/00 601 31/00 G01 33/16 flow offluid into andout of the sample chambers and a com- [58] Fie'ld 23/253230B 259 254 E mon circulator system forcirculating fluid past theelectrode 23/255 E; 204/195 T, 195 P; 324/29, 30

. assemblies and sample chambers to maintain the sample chambers andelectrode assemblies at a pre-established temperature.

9 Claims, 8 Drawing Figures Patented April 25, 1912 6 Sheets-Sheet 1 FIGPatentd A ril 25, 1972 3,658,478

6 Sheets-Shoot 2 FIG 2 Patented April 25, 1972 3,658,478

6 Sheets-Sheet 5 Patented April 25, 1972 3,658,478

6 Sheets-Sheet 6 6 PEP/005 7/ 2 72;

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FLUID ANALYZING APPARATUS SUMMARY OF INVENTION This invention relates toanalysis apparatus and more particularly to apparatus for analysis offluid samples. It has particular application to apparatus for theanalysis of parameters of precious fluids such as blood.

Frequently, an accurate measurement of one or more constituents of afluid sample is desired. For example, the values of one or more gaseousconstituents of a sample of blood may be significant. Such informationmay be used for a variety of purposes, including the obtaining ofdiagnostic information or life support controls. In particularinstances, the pH, Pco and P values of blood specimens provide importantinformation concerning the patients health, and it is an object of thisinvention to provide novel and improved instrumentation systems forthese purposes. Another object of the invention is to provide novel andimproved instrumentation systems which enable simplified analysis offluidsamples.

Another object of the invention is to provide novel and improvedapparatus that is easy to operate and provides accurate analyses ofconstituents of precious fluids such as blood.

Still another object of the invention isto provide novel and improvedanalysis apparatus for simultaneously analyzing a plurality of gases ina fluid.

Still another object of the invention is to provide novel and improvedapparatus for automatically analyzing fluid samples.

A further object of the invention is to provide novel and improvedapparatus for providing precise measurements of constituents of fluidsamples in an automated manner.

In accordance with a feature of the invention there is provided a fluidsample analysis instrument having a plurality of sample chambers, eachsample chamber having an inlet and an outlet, and an electrode assemblyfor sensing a constituent of a sample held in the sample chamber. Eachelectrode assembly produces an output signal as a function of aconstituent of interest of the sample in its chamber. A common pumpsystem applies reduced pressure to the sample chambers to produce flowof fluid into and out of the sample chambers and a common 'circulatorsystem circulates thermostatically controlled fluid past the electrodeassemblies and the sample chambers to maintain the sample chambers andelectrode assemblies at a pre-established temperature.

In accordance with another feature of the invention, a gas analysisinstrument has a sample chamber with an inlet and an outlet, and anelectrode assembly for sensing a gaseous constituent of a sample held inthe sample chamber. The electrode assembly includes a selectivelypermeable membrane disposed for exposure to the sample in the samplechamber and output circuitry for producing an output signal as afunction of a gas of interest permeating through the membrane of theelectrode assembly. The instrument also has a sample inlet, acalibrating fluid inlet, a cleaning fluid inlet. A first valve isconnected to the inlet of the sample chamber for controlling flow offluid to the sample chamber and has a first position for connecting thesample inlet to the sample chamber inlet, a second position forconnecting the calibrating fluid inlet to the sample chamber inlet, anda third position for connecting the cleaning fluid inlet to the samplechamber inlet. A second valve is connected to the outlet of the samplechamber and has a first position for connecting the sample chamber to apump, a second position for connecting the sample chamber to theatmosphere, and a third position for blocking the outlet of the samplechamber. A sequencer controls the operation of the two valves. Thesequencer is arranged to place the second valve in a fast flow modeduring a cleaning sequence facilitating rapid, efficient cleaning, in aslow flow mode during a sample induction sequence enabling the system toaccurately analyze small samples of precious fluid in the data mode, ina vent mode during a calibration sequence so that calibrating gas can beflowed through the sample chamber with a slight positive pressure thusfacilitating calibration of the electrode assembly and in an inhibitmode during standby. The

sequencer is operative in response to a first request for controllingthe first and second valves to channel cleaning fluid and thencalibrating fluid through the sample chamber in a calibrating sequence;and in response to a second request for drawing sample into the samplechamber for sensing by the constituent sensors during a sample measuringinterval. The sequencer further includes control for optionallyextending the duration of a sample measuring interval permitting theposition of the sample in the chamber to be adjusted and readings ofdesired accuracy to be easily obtained. Control logic responds to pushbutton commands and visual signals indicate the progress of theanalysis.

A particular embodiment of the invention incorporates sensors formeasuring Pco and P0 of a blood sample in one sample chamber and asensor for measuring pH in a second sample chamber. The typical samplevolume required for all three measurements is less than 0.4 milliliters.Transparent sample chambers are provided so that the sample is directlyvisible in each chamber. The instrument provides data about one minuteafter initiation of the data sequence, the data being digitallydisplayed on suitable outputs. In addition, the output signals may beapplied to a data acquisition system if desired.

' The invention provides an instrument for analyzing constituents of afluid sample, such as pI-I, Pco and P0 in an automated manner. Samplesare drawn automatically or manually by a peristaltic pump into themeasuring chambers. Twenty-five samples per hour may be analyzed with acalibration sequence prior to each sampling.

Other objects, features, and advantages of the invention will be seen asthe following description of a particular embodiment progresses, inconjunction with the drawings, in which:

FIG. 1 is a perspective view of a blood gas analysis system constructedin accordance with the invention;

FIG. 2 is a sectional view, taken along the line 2-2 of FIG. 1 showingdetails of the sample chamber and measuring electrodes employed in thesystem shown in FIG. 1;

FIG. 3 is a diagram showing the fluid flow paths and inter connectionsemployed in the system shown in FIG. 1;

FIG. 4 is a diagrammatic view of the readout circuitry;

FIG. 5 is a logic diagram of the sequencer logic employed in the systemshown in FIG. 1; and

FIGS. 6-8 are timing diagrams indicating the operation of the system inthe standby, calibrate, and sample (data) modes, respectively.

DESCRIPTION OF PARTICULAR EMBODIMENT A perspective view of a blood gasanalysis instrument is shown in FIG. 1. The instrument includes a base10 having a first section (normally enclosed with a removable panel (notshown)) which supports a transparent sample chamber structure 12disposed between two water jacket sections 14, 16. Housed in waterjacket section 14 is a p0 electrode assembly 18 (FIG. 2) and housed inwater jacket section 16 is a pCt) electrode assembly 20 (FIG. 2). Alsomounted on base 10 is a pH electrode assembly which includes a junctionassembly 22, a reference electrode 24 disposed in one section of thejunction assembly 22 and a pH electrode assembly 26 arranged fordisposition in portion 28 of junction assembly 22. Chamber 30 receiveselectrode assembly 26 when that assembly is not in use.

Also mounted on base 10 is a heater 30, a three channel peristalic pump32 (shown in FIG. 1 with the PVC tubing removed); a manually operatedperistalic pump 34; a four way pump control valve 36; a three way inletcontrol valve 38; two bubble chambers 40, 42; a gas selector switch 44;a water circulator 46; and three needle valve assemblies 50, 52, 54.Projecting forwardly of the panel is a replaceable sampling tip 56. Atthe rear of the housing are a set of fluid connections; high" gasconnection 60, "low gas connection 62, equilibrate gas connection 64,waste connection 66, flush connection 68, and vent connection 70.

On the front panel of the instrument are a set of seven indicatorsand/or controls: a data ready indicator and entry button 80, atemperature indicator 82, a wash indicator 84, a membrane failureindicator 86, a standby mode indicator and button 88, a calibrate modeindicator and button 90, and a sample mode indicator and button 92.Above the set of lamps and buttons are three digital displays, a pHdisplay 100, a pCO, display 102 and a p display 104. A balance control106, 108 and 110 is associated with each display. In addition, thesystem includes slope and zero controls on the left wall of the housing(not shown in FIG. 1).

With reference to FIG. 2, the p0 electrode 18 produces a current at aconstant polarizing voltage which is directly proportional to thetension of oxygen'diffusing to the reactive cathode surface of theelectrode. The 0.001 inch diameter cathode wire 106 is sealed in a glassenvelope 108 so that only its tip 1 is exposed at the end of theelectrode. This reactive surface 110 is covered by a polypropylenemembrane 112 which is permeable to oxygen but not to contaminants andreducible ions of the sample. To provide electrons for the cathodereaction, a silver/silver chloride anode 114 is incorporated in theelectrode and housed in an electrolyte chamber 1 16.

The pCO electrode 20 includes a pH sensitive glass membrane 120 at itstip and forming an end wall of an inner chamber 122 in which is housed asilver/silver chloride electrode 124. The outer chamber 126 is filledwith a pCO electrolyte and contains a silver/silver chloride referenceelectrode 128. Disposed over the end of the electrode assembly is anylon membrane 129 and a silastic membrane 130 that is permeable tocarbon dioxide gas but not to ions.

The membrane covered tip of each electrode is disposed in sample chamber132 for direct exposure to the sample that is supplied to chamber 132through inlet 134 and removed from that chamber through outlet 136.Water jacket sections 14 and 16 are filled through plugs 138, 140 andthe sample chamber and electrodes are maintained, at a thermostatedtemperature by circulation (by circulator 46 in FIG. 1) of athermostating fluid that is maintained at a preset temperature,typically 37 C., by heater 30 (FIG. 1) into chamber assembly 12 and thenthrough water jacket sections 14 and 16. Electrode 142 applies a signalto chamber 132 for sensing membrane integrity.

The pH electrode system (FIG. 3) includes a capillary section 148 of pHsensitive glass in which the sample is drawn from line 150 either byvacuum applied via tube 152 by pump 32 or by operation of rollerassembly 154 (FIG. 1). A silver/silver chloride half cell is disposed inan electrolyte chamber that surrounds the capillary tube 148. Areplaceable sampling tip 156 is pressed onto the tip of the measuringelectrode assembly and surrounding the measuring electrode is a waterjacket 158. The reference electrode 24 contains a saturated calomel halfcell, and the junction assembly 22 contains a saturated KC] solution andestablishes electrical contact between the reference electrode 24 andthe sample in the capillary of the measuring electrode 26 when themeasuring electrode assembly 26 is disposed in receptacle 28.

A diagram of the circulation paths in the instrument is shown in FIG. 3.Analyzed gases of known oxygen and carbon dioxide content are used ascalibration standards for the electrode assembly 18 and 20. A high" gasmixture 160 of about l0 percent carbon dioxide and the remaindernitrogen is used to slope the pCO, electrode assembly 20 and zero the p0electrode assembly; and a low gas mixture 162 of about 5 percent C0,, 12percent 0, and the balance nitrogen is used to slope the p0 assembly 18and balance the pCO: assembly 20 and is routinely used to simulate thecarbon dioxide tension of normal arterial blood. The high" gas supply160 is connected through coupling 60, needle valve 50, fluid diode 164,and bubble chamber 40 to selector valve 44, and the low" gas supply 162is connected through coupling 62, needle valve 52, diode 166, and bubblechamber 42 to the selector valve 44. That valve has two positions, afirst position in which bubble chamber 42 is connected via outlet line168 to valve inlet port 170 and a second position in which bubblechamber 40 is connected to outlet line 168. The gases are humidified bypassing through the bubble chambers 40, 42 to avoid drying the membranes112, 130 during calibration. Each bubble chamber is filled withdistilled water and each calibrating gas is passed through therespective chamber at a pressure of about 3 p.s.i.g. for equilibrationpurposes. Flow rates are controlled by the needle valves 50, 52 toprovide a bubble rate through each chamber of two bubbles per second.

Thermostated water typically at a temperature of 37 C.- is circulated bycirculator 46 through heater 30 and into the sample chamber structure 12for flow to the water jackets 14 and 16 that surround the sample chamber132 and electrodes 18 and 20. Water from jacket 14 is returned to thecirculator 46 over line 220 while water from jacket 16 is transferredover line 222 to the water jacket 158 of the pH electrode assembly 26and then returned to the circulator 46 over line 224.

Gas from supply 162 is also coupled through needle valve 54, solenoidoperated gas saver valve 172 and coupling 64 to a flush solution bottle174 which stores a cleaning solution that is circulated through thesample chamber 132 and the sample lines to remove protein deposits andprevent occluding of those lines. Flush solution from reservoir 174 issupplied through coupling 68 and line 176 to a second input port 178 ofinlet valve 38. Fluid from sampling tip 56 is also supplied over line180 to a third inlet port 182 of valve 38. The outlet port 184 of valve38 is connected over line 186, through heater 30 and the inlet line 134to sample chamber 132. The outlet line 336 is connected to inlet port188 of pump valve 36 and to the inlet port 189 of manual pump 34.

Pump valve 36 has a vent outlet port 190 connected via line 192 andconnector 70 to waste container 194; an outlet port 196 connected vialine 198 to the slow section 200 of pump 32 (which pumps at a rate ofabout 25 microliters per second); and outlet port 202 connected via line204'to the fast section 206 of pump 32 (which pumps at a rate of about200 microliters per second). The third section 208 of pump 32 has aninput over line 154 from the pH electrode assembly 26 and assists sampleinduction and flushing of that assembly. The outlet of each section ofthe pump is connected via a common line 212 and connector 66 to thewaste container 194, and similarly the outlet 214 of manual pump 34 isconnected via line 216 and connector 66 to the waste container 194.

The gas saver valve 172 is open at all times other than when theinstrument has completed the standby flush cycle and the flush solutionis equilibrated with the low gas 162 to minimize shock to the electrodesand to maintain them close to normal sample equilibration values so thata rapid electrode response time during sample analysis is provided.

With reference to FIG. 4, the circuitry 250 senses the potentialdeveloped between the pH sensitive glass half cell 26 and the referenceelectrode half cell 24 and translates that 'mto an output signal appliedon line 252 to the digital display 100. A pl-I balance control 106enables a small potential difference, caused by such things as curvatureof the pH glass, to be cancelled out by adding the same potential withopposite polarity to provide a zero reading (e.g. pH 6.840) on thedisplay 100. With a second buffer of pH 7.384, the gain of the amplifiermay be adjusted with slope control 112 until the display 100 reads pI-I7.384.

A constant polarizing voltage is applied across the cathode and anodeelectrodes of the O electrode 18 and the translating circuitry 254senses the resulting current flow and translates that signal into anoutput on line 256 for application to display 102. The translatingcircuit 254 has similar balance and slope adjustments 108, 114. The high(zero concentration 0 gas is used for balance of the oxygen electrodeand slope is adjusted with the low 12 percent 0,) gas.

The pCO, electrode system 20 is an adaptation of the pH electrode as theCO diffused through membrane 130 changes the pH of the electrolytebehind that membrane. The output voltage from the pCO electrode 20 isexponentially related to the partial pressure of carbon dioxide and thetranslation circuitry 258 includes an antilog conversion circuit 260 andgenerates an output signal on line 262 which is applied to display 104.In like manner the display is calibrated utilizing the balance and slopecontrols 110, 116, respectively. The low (5 percent CO gas is used forbalance and the high (l0 percent CO gas is used to adjust the sloperesponse of the circuitry.

Convert/hold logic 270 responsive to sequencer 272 locks the displays102 and 104 at specified times in the operating cycle.

A diagram of the control logic is shown in H0. 5. Depression of apushbutton 88B, 90B, 92B sets Status circuit 300 to produce acorresponding output on its output lines 302, 304, 306 and 308.Depression of any pushbutton also applies a reset signal via Reset logic310 for resetting logic elements in the circuitry. The reset circuit 310produces output pulses on cable 314 a 7 millisecond pulse to resetcounter 324 and a 30 millisecond pulse to reset the clock 318 and flipflops 328,338. Sequencer logic includes Clock 316, Divide circuit 318and BCD Counter and Decoder circuit 320. Circuit 320 produces outputsT0, T1, T1, T2, T4 and T8. Clock 316 produces output pulses on line322.at 1 second intervals. Divide circuit 318 produces pulses on line324 at 4 second intervals so that the mode of the counter-decoder ischanged at 8 second intervals. Thus, for example, the T1 level existsfor 8 seconds. An output from OR circuit 326 terminates the productionof signals by the divide circuit 318 until that circuit is reset by asignal from the reset circuit 310. Optionally, either analog or binarycoded decimal outputs of the data applied to displays 100, 102 and 104may be transferred to a data acquisition system. A signal on line 327inhibits the generation of clock pulses in a computer latch operationuntil the data acquisition system signals that it has acquired the data.

The control logic also includes extend logic that includes Extend flipflop 328 and two AND circuits 330, 332; and end sample logic thatincludes End Sample flip flop 338 and integrator 340.

The Extend flip flop 328 is conditioned by an output signal on line 306to respond to a further depression of pushbutton 928 through AND circuit330 and OR circuit 332 and to be cleared by the T1 pulse through ORcircuit 332. The End Sample flip flop 338 is conditioned to be set by anEXTEND signal from flip flop 328 over line 334 and is set at T10 time byintegrating the T8 pulse that is applied to integrator 340. End Samplesignal on line 344 from flip flop 338 is applied to status circuit 300to change the status from Sample mode to Calibrate mode, terminating theoutput signal on line 306 and producing output signals on line 304 and308.

AND circuit 350 produces an output on line 352 in response to the CALmode signal on line 304 and an END SAMPLE output from flip flop 338 online 342; and AND circuit 354 produces an output on line 356 in responseto the CAL mode signal on line 304 and the T8 signal from counterdecoder320. AND circuit 358 produces an output on line 360 in response to SBYmode signal on line 302 and the T4 signal from decoder 320; AND circuit362 produces an output on line 364 in response to the SAMP mode signalon line 306 and the T1 signal; and OR circuit 366 produces an output online 368 in response to an input from either AND circuit 358 or 362.

The control logic further includes a set of four AND circuits 370, 372,374 and 376 which control the drive 378 for the pump valve 36; and a setof three AND circuits 380, 382 and 384 which control the drive 386 forthe inlet valve 38. A feedback signal from each valve drive via feedbackcircuits 379, 388, respectively, is applied to the corresponding ANDcircuit to stop operation of the drive when the valve has reached thecorresponding position.

The Sample lamp 92L is energized in Sample mode by the SAMP signalapplied to AND circuit 390 from line 306 of status circuit 300. A secondinput to AND circuit 390 is from OR circuit 392 which has a first inputfrom the clock 310 at one second intervals and produces a flashingenergization of lamp 921. uiiless bverridden, a second input from theEX- TEND signal on line 336 by which lamp 92L is maintained continuouslylighted after the EXTEND flip flop 388 is set until it is cleared by theT1 pulse; and T1 and T2 inputs from circuit 320. (Modifications ofthistiming may be provided as desired for particular operationalpurposes.)

The Wash lamp 84 is energized when the End Sample flip flop 338 is setby a signal on line 344 applied to AND circuit 390 for the next twocycle times (T0 and T1). (Again the duration of this signal may bevaried as desired.)

The Data lamp 80 is energized via OR circuit 396 when the End Sampleflip flop 338 is set or, in a Calibrate cycle, by the output at the endof the calibrate cycle from AND circuit 354. The Calibrate lamp 90L isenergized via OR circuit 398 by an output from AND circuit 350 at thestart of the Calibrate cycle or in the Sample cycle when the End Sampleflip flop is cleared, by an output from AND circuit 354. The converthold logic 270 is conditioned by a signal from OR circuit 400 whichresponds to a signal from AND circuit 354 at the end (T8 time) of theCalibrate mode and a signal from AND circuit 362 during the sample mode(T1 time).

Further understanding of this control logic may be had with referencetoFIG. 5 and the timing diagram in FIG. 6. When Standby button 883 isdepressed, Status circuit 300 produces an output on line 302 whichlights Standby lamp 88L and an output on line 308. At the same time asignal is applied to reset circuit 310 to generate on cable 314 a 7microsecond pulse to reset the BCD Counter and Decoder 320 and a 30microsecond signal to reset the clock 316, the Divide circuit 318 andflip flops 328 and 338. The next signal from divider 318 triggersCounter-Decoder 320 to produce the T1 signal which is passed through ANDcircuit 372 to energize valve drive 378 and move the pump valve 36 tothe fast position, connecting inlet line 188 with outlet line 202. Whenvalve 36 reaches this position, a signal from the feedback circuit 359removes a conditioning input from AND circuit 372, de-energizing valvedrive 378. The T1 signal is also applied to AND circuit 382 and valvedrive 386 is energized to move inlet valve 38 to the sample position,connecting sample line 180 to output line 186 (feedback circuit 388de-energizing pump drive 356 when that position is reached). In thiscondition air is drawn in through sample line 180. ln the next cycle,the Counter-Decoder 320 generates a T2 pulse and AND circuit 380,conditioned by the previously present SAMP signal on line 308, operatesvalve drive 380 to move the inlet valve 38 from the sample position tothe flush position, connecting line 176 to outlet line 186. In thiscondition, flush solution is drawn through the cuvette chamber 132.

When Counter-Decoder 320 generates the T4 pulse, AND circuit 358 isconditioned and its output is applied through OR circuit 366 to energizeAND circuit 370 and operate the pump valve drive 378 to move valve 36 tothe inhibit position, sealing flush solution within the tubing 134, 136in the cuvette chamber 132. The electrode membranes 112, 130 are thuskept moist by the equilibrated flush solution, and the instrument can beleft overnight in this mode. The output from AND circuit 358 is alsoapplied through OR circuit 326 to terminate the production of pulsesfrom Divide circuit 318 and v also over line 404 to de-energize the gassaver valve 172 and to turn off the pump drives and the display. In thismode, the only lamp that is left energized is the Standby lamp 88L.

With reference to FIGS. 5 and 7, in preparation for an analysis, theinstrument is calibrated with two analyzed gases from sources 160 and162. Depression of button 903 applies a signal to the Status circuit 300to produce an output on lines 304 and 308 and also applies a signal tothe Reset circuit to reset the control logic. The output on line 304 isapplied to AND circuits 350, 354, 374, and 384. As End Sample flip flop338 is not set, AND circuit 350 has an output and, via OR circuit 398,lights Calibrate lamp 90L.

The output on line 308 is applied to AND circuits 372 and 380. WhenCounter-Decoder 320 generates the T1 signal, AND circuit 372 has anoutput which operates drive 378-to place the pump valve 36 in the fastposition andAND circuit 382 has an output which operates inlet valvedrive 386 to place valve 38 in the sample position. Air is drawn inthrough the cuvette chamber until the T2 signal is generated. At thattime, AND circuit 380 has an output which moves inlet valve 38 to theflush position, and flush solution is pumped through the sample chamber132 for two time periods. With the generation of the T4 signal, anoutput from AND circuit 384 moves inlet valve 38 to the calibrating gasposition, connecting input line 168 with output line 186, and an outputfrom AND circuit 374 moves pump valve 36 to the vent position. Thecalibrating gas, as selected by the position of valve 44, then flowsthrough the sample chamber 132 for equilibration with the electrodes andpermitting the instrument to be calibrated as above described. The T8pulse from Counter- Decoder 320 is applied to AND circuit 354 andenergizes the Data lamp 80 via OR circuit 396 and the Convert Hold logic270 via OR circuit 400 to unclamp the displays 102, 104. This outputsignal is also applied through OR circuit 326 to terminate production ofoutput signals by Divider 318. In this mode, each calibrating gas may bechanneled through the cuvette chamber 132 as selected by valve 44, andthe operator may slope and balance the electrode assemblies 18 and 20with controls 108, 110, 114 and 116. The instrument remains in thisstate until another mode button is depressed.

When the response of the electrodes has been calibrated satisfactorily,the instrument is ready for sampling. With reference to FIGS. and 8,with the sample tip 56 immersed in a blood sample to be analyzed, theSample button 92 is depressed. In response to that operation, the Statuscircuit 300 produces an output on line 306 and the signal is appliedthrough Inhibit circuit 312 to Reset circuit 310 which generates resetsignals on cable 314.

When Counter-Decoder 320 produces a T1 signal, pump valve 36 ispositioned in slow mode in response to an output from AND circuit 376and inlet valve 38 is positioned in sample position in response to anoutput from AND circuit 382. Blood sample is drawn slowly into thesample chamber 132 during the first time period (Tl). With thegeneration by Decoder 320 of the T1 signal, AND circuit 362 produces anoutput which is applied through OR circuit 366 and AND circuit 370 tomove pump valve 36 to the inhibit position, stopping the pumping action.Due to the provision of a fluid capacitor between chamber 132 and valve36, the sample continues to be drawn into the cuvette chamber at anexponentially decreasing velocity for another ten seconds, facilitatingequilibration of the membranes and electrode assemblies 18, with theblood sample. At the end of the T2 cycle, lamp 92 commences to flash atone second intervals in response to signals from the Clock 318 appliedthrough OR circuit 392 and AND circuit 384, indicating that the sampletip 56 may be removed from the sample container. When Counter-Decoder320 generates the T8 signal, that signal conditions Integrator 340 andits output at T10 time sets End Sample flip flop 338. The output on line344 from End Sample flip flop 338 is applied to Status circuit 300 tochange its condition from sample mode to calibrate mode, terminating anoutput on line 306 and producing outputs on lines 304 and 308. Theoutput from the End Sample flip flop is also applied to data lamp 80 via0R circuit 396 and wash lamp 84 via AND circuit 394. At this time theCounter-Decoder 320 is producing the T0 signal and the wash lamp 84 isenergized until the end of T1 time (2 clock periods), indicating thatthe sample tip 56 should be placed in the saline cleaning solution forintroduction of that solution through the sample line 180 and into thecuvette chamber 132. With the termination of the signal from AND circuit362, the output of OR circuit 400 tenninates the Convert Hold circuit270 clamps the displays. Also Sample lamp 92L is de-energized.

The Calibrate cycle is now repeated automatically with cycling of pulsesfrom Counter-Decoder 320 to flush the sample chamber 132 (T2-T4 time)and then allowing calibrating gas to flow into the sample chamber 132.At T8 time the displays are released and the calibrating lamp 901.. isenergized so that the operator may check the instrument balance prior tothe next sample without pressing the calibrate button 9013 again.Another sample cycle may be run merely by inserting the sample in thecleaned sample tip and depressing the Sample button 928.

If for any reason the normal sample interval allotted for equilibrationof the sample is insufficient, a ten cycle extension period may beobtained during the interval when Sample lamp 92L is flashing merely bypressing the sample button 928 again. In this mode, the output on line306 is applied to Inhibit circuit 312 and prevents this second signalfrom being applied to the reset circuit 310. The signal is applied toAND circuit 330 which has a conditioning input from the Extend flip flop328 on line 334 and the output of AND circuit 330 is passed by ORcircuit 332 to set flip flop 328 which produces an output on line 336 tocondition Inhibit circuit 402 and to remove the conditioning level thatis applied to flip flop 338 on line 334. The output on the Extend flipflop output line 336 is also applied through OR circuit 392 to terminatethe flashing of Sample lamp 92L and maintain it continuously energized.This mode permits the operator to adjust the position of the sample inchamber 132 using manual pump 34 or to extend the Sample equilibrationperiod. As the End Sample flip flop 338 is not set by the integrated T8pulse, the sample cycle is repeated except that the T1 signal isinhibited by Inhibit circuit 404. With the generation of the T1 signal,flip flop 328 is cleared, reestablishing a conditioning input for ANDcircuit 330 and a conditioning input for flip flop 338. At the end ofthe T2 interval, Sample lamp 92L commences flashing again, indicatingthat the displays are active and responding to the sample in chamber132. Unless the Sample button 92 is pressed again, the T1 signal will begenerated in the next cycle and allow an End Sample signal to begenerated on line 344 which lights the data lamp and initiates sampleremoval and cleaning of the cuvette chamber 132 in preparation forcalibration and running of the next sample.

lnforrnation concerning further details of this system may be had withreference to the following copending patent applications assigned to thesame assignee as this application:

Inventor Title S.N. Filing Date Huddad ct a]. Electrode Assembly 27.l94Apr. 7. I970 Blackmer Sensor Instrumentation 27,198 Apr. 7, I970Blackmer Fault Sensing Instrumentation 27,I97 Apr. 7, I970 Spergel etal. Fluid Handling Apparatus 27.I99 Apr. 7, I970 Neuwelt Fluid SampleAnalyzing Apparatus 27,l93 Apr. 7. I970 While a particular embodiment ofthe invention has been shown and described, various modificationsthereof will be apparent to those skilled in the art and therefore it isnot intended that the invention be limited to the disclosed embodimentor to details thereof and departures may be made therefrom within thespirit and scope of the invention.

What is claimed is:

1. A precious fluid sample analysis instrument comprising a plurality ofsample chambers, each said sample chamber having fluid jacket structure,an inlet and an outlet, an electrode assembly associated with eachsample chamber for sensing a constituent of a sample held in the samplechamber, each said electrode assembly producing an output signal as afunction of a constituent of interest of the sample in its chamber, aplurality of sampling tip structures, each said sample chamber inputbeing connected to a separate sampling tip structure, a common pumpsystem connected directly to each said sample chamber outlet forapplying reduced pressure to said sample chambers to produce flow offluid into and out of said sample chambers, separate manually responsivecontrols for adjusting the position of fluid in each said samplechamber, and a common circulator system for circulating thermostaticallycontrolled fluid through said sample chamber jacket structures past saidelectrode assemblies and said sample chambers to maintain the samplechambers and electrode assemblies at a pre-established temperature.

2. The instrument as claimed in claim 1 wherein one electrode assemblyassociated with a first sample chamber produces an output signal as afunction of the pH of the sample in its sample chamber and the electrodeassembly associated with a second sample chamber produces an outputsignal as a function of the partial pressure of a predetermined gas inthe sample in its sample chamber.

3. The instrument as claimed in claim 2 wherein the electrode assemblyassociated with said second sample chamber includes a selectivelypermeable membrane disposed for exposure to the sample in said secondsample chamber and output circuitry for producing an output signal as afunction of a gas of interest permeating through said membrane.

4. A blood gas analysis instrument comprising a sample chamber,aplurality of electrode assemblies for sensing gaseous constituents of asample held in said sample chamber, each said electrode assemblyincluding a selectively permeable membrane disposed for exposure to thesample in said sample chamber and output circuitry for producing anoutput signal as a function of a gas of interest permeating through themembrane of the electrode assembly,

two sources of calibrating fluids, a first valve connected to said twosources of calibrating fluids for selectively applying one of saidcalibrating fluids to an outlet line, a source of cleaning fluid, arelatively low capacity pump, a higher capacity pump,

a second valve connected to the inlet to said sample chamber forcontrolling flow of fluid to said sample chamber, said second valvehaving a first position for connecting a sampling passage to said samplechamber, a second position for connecting said outlet line to saidsample chamber, and athird position for connecting a source of cleaningfluid to said sample chamber, 7

a third valve connected to the outlet of said sample chamber, said thirdvalve having a first position for connecting the sample chamber to saidrelatively low capacity pump, a second position for connecting saidsample chamber to said higher capacity pump, a third position forconnecting said sample chamber to the atmosphere, and a fourth positionfor blocking the outlet of said sample chamber, manually operable pumpconnected to said sample chamber for displacing fluid in said samplechamber,

a circulator for circulating a thermostatically controlled fluid pastsaid electrode assemblies and said sample chamber to maintain the samplechamber and electrode assemblies at a pre-established temperature,

fourth valve connected between one of' said sources of calibrating fluidand said source of cleaning fluid for introducing calibrating gas intosaid cleaning fluid to reduce shock to the membranes of said electrodeassemblies during exposure to said cleaning fluid in a flushingoperation,

and a sequencer for controlling the operation of said second and thirdvalves,

said sequencer having a first mode of operation in response to a firstrequest for operating said second valve to connect said sample chamberto said cleaning fluid while said third valve is connected to saidhigher capacity pump; a second mode of operation in response to a secondrequest for positioning said second valve to sequentially connect saidsample chamber to said sample line, said cleaning fluid and acalibrating gas while said third valve is connected to said highercapacity pump and then switching said third valve to said fourthposition; and a third mode of operation in response to a third requestfor positioning said second valve to connect said sample chamber to saidsample line while said third valve is connected to said low capacitypump and then swltchmg said third valve to said fourth position for asample measuring interval.

5. The instrument as claimed in claim 4 wherein said sequencer includescontrol logic for providing visual indication of the operating mode ofthe instrument and means to modify said visual indication during saidsample measuring interval. I

6. The instrument as claimed in claim 5 wherein said control logicincludes a status circuit having outputs indicating the operating modeof said instrument, and firstbistable means responsive to the end ofsaid sample measuring interval for changing the output of said statuscircuit.

7. The instrument as claimed in claim 6 wherein said control logicfurther includes logic for optionally deferring initiation of saidcalibration sequence for an interval of time to extend the duration ofsaid sample measuring interval, said calibration sequence deferringlogic including second bistable means responsive to an extend requestfor inhibiting the operation of said first bistate means to the end ofsaid sample measuring interval.

8. The instrument as claimed in claim 7 and further including a secondsample chamber having an inlet and an outlet, a second electrodeassembly associated with said second sample chamber for sensing aconstituent of a sample held in said second sample chamber, saidelectrode assembly producing an output signal as a function of aconstituent of interest of the sample in said second chamber, a commonpump system for applying reduced pressure to both sample chambers toproduce flow of fluid into and out of said sample chambers and a commoncirculator system for circulating said thermostatically controlled fluidpast said electrode assemblies and said sample chambers to maintain thesample chambers and electrode assemblies at a preestablishedtemperature.

9. The instrument as claimed in claim 8 wherein said sequencer in saidfirst mode of operation sequentially operates said second valve toconnect said sample chamber to said cleaning fluid while said thirdvalve is connected to said high capacity pump, and then switches saidthird valve to said fourth position and closes said fourth valve.

* IIK 3 3 UNITED STATES PATENT OFFICE CERTIFICATE OF CORRECTION PatentNO- I, 251 [nvent0r( Philip Spergel et 8.].-

It is certified that; error appears :Ln the above-identified patent andthat said Letters Patent are hereby corrected as shown below:

7 Column 2 line 72', delete the dash after the quotes;

Column I, line 8, the numeral-should read --3 l/2--;

Column 5, line- 21, "T1" (second occurrence) shouldbe 1 Tl--' line 13,"EXTEND" should be --E X TEN D I lines 5152, "END SAMPLE should-be -EI\ID S MPLE";

Column 6 I I line l; "T1" should be --T} (first occurrence) line21,"'Il" should be --'Il--; line 45, "SAME". should be -SAMP-;

Column 7', line 41 "Tl" should be -'TT--;

' Column 8-, line 28, "T1" should be --'TT-.

Signed and sealed this 27th dayof F b 1973 (SEA-L) Attest:

- EDWARD M. FLETCI-IER,JR.

Attesting Officer ROBERT GOTTSCHALK Commissioner of Patents

2. The instrument as claimed in claim 1 wherein one electrode assemblyassociated with a first sample chamber produces an output signal as afunction of the pH of the sample in its sample chamber and the electrodeassembly associated with a second sample chamber produces an outputsignal as a function of the partial pressure of a predetermined gas inthe sample in its sample chamber.
 3. The instrument as claimed in claim2 wherein the electrode assembly associated with said second samplechamber includes a selectively permeable membrane disposed for exposureto the sample in said second sample chamber and output circuitry forproducing an output signal as a function of a gas of interest permeatingthrough said membrane.
 4. A blood gas analysis instrument comprising asample chamber, a plurality of electrode assemblies for sensing gaseousconstituents of a sample held in said sample chamber, each saidelectrode assembly including a selectively permeable membrane disposedfor exposure to the sample in said sample chamber and output circuitryfor producing an output signal as a function of a gas of interestpermeating through the membrane of the electrode assembly, two sourcesof calibrating fluids, a first valve connected to said two sources ofcalibrating fluids for selectively applying one of said calibratingfluids to an outlet line, a source of cleaning fluid, a relatively lowcapacity pump, a higher capacity pump, a second valve connected to theinlet to said sample chamber for controlling flow of fluid to saidsample chamber, said second valve having a first position for connectinga sampling passage to said sample chamber, a second position forconnecting said outlet line to said sample chamber, and a third positionfor connecting a source of cleaning fluid to said sample chamber, athird valve connected to the outlet of said sample chamber, said thirdvalve having a first position for connecting the sample chamber to saidrelatively low capacity pump, a second position for connecting saidsample chamber to said higher capacity pump, a third position forconnecting said sample chamber to the atmosphere, and a fourth positionfor blocking the outlet of said sample chamber, a manually operable pumpconnected to said sample chamber for displacing fluid in said samplechamber, a circulator for circulating a thermostatically controlledfluid past said electrode assemblies and said sample chamber to maintainthe sample chamber and electrode assemblies at a pre-establishedtemperature, a fourth valve connected between one of said sources ofcalibrating fluid and said source of cleaning fluid for introducingcalibrating gas into said cleaning fluid to reduce shock to themembranes of said electrode assemblies during exposure to said cleaningfluid in a flushing operation, and a sequencer for controlling theoperation of said second and third valves, said sequencer having a firstmode of operation in response to a first request for operating saidsecond valve to connect said sample chamber to said cleaning fluid whilesaid third valve is connected to said higher capacity pump; a secondmode of operation in response to a second request for positioning saidsecond valve to sequentially connect said sample chamber to said sampleline, said cleaning fluid and a calibrating gas while said third valveis connected to said higher capacity pump and then switching said thirdvalve to said fourth position; and a third mode of operation in responseto a third request for positioning said second valve to connect saidsample chamber to said sample line while said third valve is connectedto said low capacity pump and then switching said third valve to saidfourth position for a sample measuring interval.
 5. The instrument asclaimed in claim 4 wherein said sequencer includes control logic forproviding visual indication of the operating mode of the instrument andmeans to modify said visual indication during said sample measuringinterval.
 6. The instrument as claimed in claim 5 wherein said controllogic includes a status circuit having outputs indicating the operatingmode of said instrument, and first bistable means responsive to the endof said sample measuring interval for changing the output of said statuscircuit.
 7. The instrument as claimed in claim 6 wherein said controllogic further includes logic for optionally deferring initiation of saidcalibration sequence for an interval of time to extend the duration ofsaid sample measuring interval, said calibration sequence deferringlogic including second bistable means responsive to an extend requestfor inhibiting the operation of said first bistate means to the end ofsaid sample measuring interval.
 8. The instrument as claimed in claim 7and further including a second sample chamber having an inlet and anoutlet, a second electrode assembly associated with said second samplechamber for sensing a constituent of a sample held in said second samplechamber, said electrode assembly producing an output signal as afunction of a constituent of interest of the sample in said secondchamber, a common pump system for applying reduced pressure to bothsample chambers to produce flow of fluid into and out of said samplechambers and a common circulator system for circulating saidthermostatically controlled fluid past said electrode assemblies andsaid sample chambers to maintain the sample chambers and electrodeassemblies at a preestablished temperature.
 9. The instrument as claimedin claim 8 wherein said sequencer in said first mode of operationsequentially operates said second valve to connect said sample chamberto said cleaning fluid while said third valve is connected to said highcapacity pump, and then switches said third valve to said fourthposition and closes said fourth valve.